Hypotheses will be tested via a placebo-controlled double blind study using a sample of healthy men and women recruited from the community (overall n = 320). The proposed experimental study will consider oxytocin effects on a range of outcomes. These include autonomic reactivity as measured by blood pressure responses and high frequency heart rate variability (measure of vagal tone). Stress-related cardiovascular phenotypes as characterized by the patterning of ventricle contractility, vascular resistance, and cardiac output will also be assessed. Other outcomes include measures of neuroendocrine effects as measured by levels of cortisol and dehydroepiandrosterone (DHEA) hormone, subjective distress and positive affect. Participants will be randomly assigned to receive either exogenous oxytocin or placebo. They will undergo a social stress manipulation with or without social support (randomly assigned), and outcome measures will be obtained at multiple times during the experimental procedure. The experiment will test whether effects of oxytocin and social support are similar and additive, and will also compare effects of oxytocin and social support across men and women of varying ages. This multidisciplinary study uses a biobehavioral framework to examine interactions between psychological, social, and biological levels of functioning, and is informed by theories of how key early life exposures may impact health over the life course. The provision of an R21 award for this work will facilitate novel research that could have a major impact on our understanding of whether and how oxytocin influences responses to stress in humans. The proposed exploratory research will lay the groundwork for the submission of an R01 grant proposal that will have greater resources for addressing both the questions that cannot be addressed with this more limited mechanism as well as new questions that will undoubtedly arise. Ultimately we expect this project will provide a solid platform from which to launch a larger program of research aimed at identifying how positive social and emotional experiences influence adult health and longevity. A neurobiological understanding of resilience can inform efforts for both prevention and intervention of diseases or problems common in later life.